The pharmacokinetics of propranolol are complex and subject to considerable interpatient variability. Hepatic uptake of propranolol appears to be a dominant factor in determining the pharmacokinetics in the human. Preliminary calculations indicate that rat liver may be a reasonable model of the human liver in this regard. This project will study the uptake of propranolol by the isolated perfused rat liver. The perfusion conditions (e.g., temperature, oxygen concentration and presence of general metabolic inhibitors) will be varied to determine whether uptake involves active transport or merely simple physical binding. The effects of other drugs (e.g., cations, amines, and anions) on uptake of propranolol will be characterized with respect to competitive or noncompetitive inhibition of the high or low affinity uptake process. These drug effects should help elucidate the nature of the uptake processes as well as providing guidelines for avoidance of drug interactions and adverse effects in clinical use of propranolol.